Dr. Christin Gasch, Ph.D., Head of Process Development, at Vibalogics Cuxhaven explores the challenges hindering the successful expansion of oncolytic viral therapy and explains what is needed in order for the approach to take its rightful place as a complement to existing treatments.
Cancer treatments, such as radiotherapy and chemotherapy, have been used for many years now. Working in combination and alongside surgery, they have been effective in decreasing the global mortality rate of cancer significantly from 142.5 (per 100,000 people) in 1990 to 121.1 in 2017.
Nevertheless, these treatments still have disadvantages for patients. Surgery is invasive, and there is a risk of post-surgical complications, while radiotherapy and chemotherapy are toxic with harmful side effects.
Oncolytic viruses (OVs) have been moving up the pharmaceutical agenda in recent years, as an exciting potential complement to traditional cancer treatments. Thanks to advances in genetic engineering, it is now possible to tailor the genome of viruses to target an explicit viral host range that is specific to that of cancer cells and improve the overall efficacy of the treatment and minimize off-target effects.
Understanding OVs
Tumor cells possess a number of mechanisms that allow them to evade the body’s natural immune system protection by masking phenotypic changes specific to that of cancer cells. However, these changes can be exploited to target OVs exclusively to cancer cells. Once the modified virus reaches and infects the target tumor cells, it replicates within and kills the host cells (a process known as oncolysis), while sparing surrounding healthy cells.
As a result of oncolysis, materials such as tumor antigens are released, which stimulate the patient’s immune system to identify the cancer cells. This can lead to both a localized and/or systemic immune response against other tumor cells within the body.
Systemic, long-term antitumor immunity to the specific cancer is then established, which triggers an immune response both to malignant growths elsewhere in the body and to potential future relapses.
Seeking the ideal OV
Despite the therapy’s incredible potential, OVs remain an emerging modality with the majority of drug developers still in early preclinical or clinical trials. Currently, there is only one US Food & Drug Administration (FDA) approved OV.
One of the key challenges holding back the development and delivery of OVs is that a single OV capable of targeting multiple cancers in most patients is yet to be found. The ideal OV possesses a number of key characteristics:
- Selective to various types of cancer cells, without affecting surrounding healthy cells
- The patient will not have pre-existing immunity to the viral platform used
- Safe to use with no risk of recombination to a wild-type virus or integration into the host genome with detrimental effects to the patient
- Simple to develop and manufacture
- Easy to transport, store and administer in a non-specialist clinical setting
It is challenging to create an OV that ticks all of the boxes above. Each cancer has a unique genetic profile, and each patient has their own unique immune response. In addition, there are manufacturing, product stability and regulatory issues that all need to be overcome to ensure success.
Nevertheless, while the search for the ideal OV continues, this sector of cancer research is growing significantly, with a vast array of therapy candidates already in development.
Overcoming challenges
Tackling development obstacles and ensuring the treatment reaches clinical trials requires expertise as well as dedicated resources.
As an OV focused contract development and manufacturing organization (CDMO), Vibalogics are uniquely qualified to support pharmaceutical companies in progressing their discoveries from development to clinical trials and beyond. With specialist infrastructure already in place to scale up production as well as expert teams, we are here to support developers in navigating the complexities of OV development.
